PHARMACEUTICAL COMPOSITIONS AND METHODS FOR MANUFACTURING ON-DEMAND SOLID DOSAGE FORMULATIONS

Abstract

A pharmaceutical composition and methods for using the pharmaceutical composition are described. The pharmaceutical composition may include a therapeutically effective amount of one or more antiviral pharmaceutically active ingredients and a pharmaceutically acceptable excipient. The pharmaceutical composition may be a solid dosage form, wherein the solid dosage form provides sustained release of the antiviral pharmaceutically active ingredient when administered as a vaginal or rectal insert.

Description

The Truvada daily oral tablet (FTC / TDF) is the only product approved as of 2012 for HIV prophylaxis. The daily Truvada tablet regimen has adherence issues due to the large number of pills. Another HIV prophylaxis product is the once-monthly dapivirine ring for women, developed by IPM. IPM is currently seeking approval from national and global regulatory authorities for the ring's use in countries where women face the highest risk of HIV infection. A third HIV prevention product in Phase III development is the long-acting (LA) injectable cabotegravir (CAB) from ViiV. The LA injectable CAB is irreversible, requires oral administration, and raises concerns about resistance due to the potential long prokinetic chain (PK) tail problem. Therefore, there is a need for an on-demand topical pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PrEP) product, which will provide more desirable options for women and men, such as on-demand topical vaginal and rectal PrEP. On-demand topical PrEP for HIV prevention has several advantages over a regimen of Ref. 317644 Daily oral PrEP, including reduced costs, limited drug toxicity, lower risk of resistance, and the potential to increase adherence. Summary of the Invention This application describes pharmaceutical compositions and methods for preparing solid dosage forms containing antiviral active pharmaceutical ingredients in the form of an insert. More specifically, this application describes solid dosage forms comprising tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) in the form of an insert. The insert formulation described herein is suitable for the administration of an antiviral drug or a combination of antiviral drugs for on-demand treatment and / or prevention of HIV, HBV, and HSV infection before and after sexual activity. This formulation composition also overcomes the chemical stability problems associated with TAF.Furthermore, antiviral drugs administered via an insert for local delivery to the vagina and / or rectum and systemic circulation are beneficial, and promising preclinical in vitro data are described here for the prevention of HIV and HSV. The insert may be a solid dosage form, such as a tablet, with instructions for easy administration. The insert described here may offer several advantages over other dosage forms for HIV, HSV, and HBV prophylaxis, such as on-demand topical drug delivery, targeted administration to the site (e.g., vaginal or rectal mucosa), improved adherence due to increased effectiveness, discreet (small) size, ease of use, simplicity, portability, and self-administration capabilities.The inserts are economical with a relatively low manufacturing cost, are safe and acceptable, and provide more tolerance with more flexible dosage options, such as before or after sexual activity. In one aspect, a pharmaceutical composition comprising a therapeutically effective amount of one or more antiviral active pharmaceutical ingredients and one or more pharmaceutically acceptable excipients is described herein, wherein the pharmaceutical composition delivers a therapeutically effective amount of the antiviral active pharmaceutical ingredient to the vaginal or rectal mucosa when administered topically. According to certain aspects, the pharmaceutical composition may be a solid dosage form, wherein the solid dosage form provides sustained release of the antiviral active pharmaceutical ingredient when administered as a vaginal or rectal insert. In another aspect, a solid dosage form comprising a therapeutically effective amount of one or more pharmaceutically active antiviral ingredients and one or more pharmaceutically acceptable excipients is described herein, wherein the solid dosage form exhibits a mucoadhesive release strength of at least 0.1 N when measured according to the test method described herein with porcine vaginal mucosa. In some formulations, the dosage form comprises approximately 1.5% to approximately 15% by weight of antiviral pharmaceutically active ingredients. In some formulations, one or more pharmaceutically active ingredients comprise an NRTI and an integrase inhibitor. In some formulations, one or more of the pharmaceutically active ingredients comprise tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG). In some formulations, tenofovir alafenamide fumarate (TAF) is present in an amount from approximately 2% to 8% TAF as a free base, and elvitegravir (EVG) is present in an amount from approximately 1.6% to 4.8%. In some embodiments, one or more pharmaceutically acceptable excipients comprise povidone. In some embodiments, the povidone comprises povidone K29 / 32, povidone K30, or a mixture thereof. In some embodiments, the one or more pharmaceutically acceptable excipients comprise a water-soluble disintegrant, such as poloxamer 188, which may be present in an amount from 0.5 to 4% by weight. In some formulations, the one or more pharmaceutically acceptable excipients comprise a filler, such as lactose, which may be present in an amount from approximately 25% to 75% by weight. In some embodiments, the one or more pharmaceutically acceptable excipients comprise a diluent such as a sugar alcohol, which may be present in an amount from approximately 5% to 30% by weight. In some embodiments, the sugar alcohol is selected from the group consisting of mannitol, glycerol, erythritol, xylitol, sorbitol, isomalt, maltitol, lactitol, and mixtures thereof. In some embodiments, the one or more pharmaceutically acceptable excipients comprise a bioadhesive polymer, such as PEG, more particularly PEG 6000 or PEG 8000, which may be present in an amount from approximately 5 to 30% by weight. In some embodiments, the one or more pharmaceutically acceptable excipients comprise a lubricant, which may be selected from the group consisting of magnesium stearate, stearic acid, sodium stearyl fumarate, glyceryl monostearate, colloidal silicon dioxide, talc, calcium stearate, and mixtures thereof. The lubricant may be present at a concentration in the range of 0.2–4% by weight, preferably 0.5–3% by weight, and most preferably 1.0–2.0% by weight. In some embodiments, the one or more pharmaceutically acceptable excipients comprise a hydrophilic excipient selected from the group consisting of hyaluronic acid, maltodextrin, dextrin, cyclodextrin, vitamin E TPGS, Pluronics, amino acids, gelatins, polyethylene glycols, poly(ethylene oxide) (PEO), poly(vinylpyrrolidone) (PVP), cellulose ethers and mixtures thereof. In some embodiments, the dosage form comprises from approximately 1.5% to approximately 15% by weight of one or more antiviral pharmaceutically active ingredients, a binder in an amount from approximately 0.5% to approximately 8% by weight, a water-soluble disintegrant in an amount from approximately 0.5% to approximately 4% by weight, and a bioadhesive polymer in an amount from approximately 5% to approximately 30% by weight. In some embodiments, the one or more antiviral pharmaceutically active ingredients comprise TAF and EVG, the binder comprises povidone, the water-soluble disintegrant comprises poloxamer 188, and the bioadhesive polymer comprises PEG 8000. In some formulations, the dosage form also includes an antibiotic. In some formulations, the antibiotic may be selected from the group consisting of tetracyclines, macrolides, lincosamides, nitroimidazoles, and mixtures thereof. In some formulations, the antibiotic may be selected from the group consisting of doxycycline, doxycycline hyclate, doxycycline anhydrous, doxycycline monohydrate, azithromycin, clindamycin, metronidazole, tinadazole, secnidazole, and mixtures thereof. In some embodiments, a method for treating or preventing a viral infection in a subject comprises administering to the subject a solid dosage form described herein. The dosage form may be administered before or after sexual activity. According to certain aspects, a method is also described for additionally treating another infection, such as a bacterial infection. In some modalities, the viral infection that is treated or prevented can be selected from the group consisting of HIV, HSV, and HBV. In some modalities, the bacterial infection that is treated can be selected from the group consisting of chlamydia, gonorrhea, bacterial vaginosis, trichomoniasis, and syphilis. In some modalities, the viral infection that is treated or prevented is HIV, HSV, or HBV, and the bacterial infection that is treated is chlamydia, gonorrhea, or syphilis. Brief Description of the Figures Figures 1A, 1B, and 1C show EVG dose response graphs for p24 production. The representation of p24 antigen expression from three different donors is shown under three different conditions: Figure 1A shows the results of co-exposure; Figure 1B shows the results of 7 hours of pre-exposure; and Figure 1C shows the results 9 hours post-exposure. Figure 2 is a graph showing EVG concentrations in infected versus uninfected CV tissues. Mean concentrations and ranges (minimum and maximum) are shown. PA = Adjusted protein. Figure 3 is a bar graph showing the activity of various antiviral drugs in a pre-exposure (-24 hours). Figure 4 is a bar graph showing the activity of various antiviral drugs in a post-exposure (+6 hours). Figure 5 is a bar chart showing anti-HSV activity for the prevention of genital herpes with various tenofovir prodrugs. Figure 6 is a graph showing the Tenofovir Alafenamide (TAF) Assay (% declared on the label) in 20 / 16 mg TAF / EVG insert in stability at 30°C / 65% RH (up to 9 months) and 40°C / 75% RH (up to 6 months). Figure 7 is a graph showing the Elvitegravir (EVG) Assay (% declared on the label) in the 20 / 16 mg TAF / EVG insert at stability at 30°C / 65% RH (up to 9 months) and 40°C / 75% RH (up to 6 months). Figure 8 is a graph showing the Cumulative Dissolution Percentage of Tenofovir Alafenamide (TAF) in the 20 / 16 mg TAF / EVG insert at stability at 30°C / 65% RH (up to 9 months). Figure 9 is a graph showing the Cumulative Dissolution Percentage of Tenofovir Alafenamide (TAF) in the 20 / 16 mg TAF / EVG insert at stability at 40°C / 75% RH (up to 6 months). Figure 10 is a graph showing the cumulative dissolution percentage of Elvitegravir (EVG) in the 20 / 16 mg TAF / EVG insert at stability at 30°C / 65% RH (up to 9 months). Figure 11 is a graph showing the cumulative dissolution percentage of Elvitegravir (EVG) in the 20 / 16 mg TAF / EVG insert at stability at 40°C / 75% RH (up to 6 months). Figure 12 is a bar graph showing the average detachment strength of CONRAD-P04 (placebo inserts) and CONRAD-P03 (20 / 16 mg-TAF / EVG inserts) from porcine vaginal tissue by mechanical testing. Figure 13 illustrates the dissolution and disintegration over time for an exemplary insert formulation (P03 (20 / 16 mg TAF / EVG)) in Simulated Vaginal Fluid (SVF) AC-3, pH 4.3 at 37°C. Figure 14 illustrates the dissolution and disintegration over time for an exemplary insert formulation (P03 (20 / 16 mg TAF / EVG)) in PBS-AC-1, pH 4.3 at 37°C. Figures 15A and 15B show examples of complete protection against HIV infection ex vivo in baseline and post-treatment cervical tissue samples from two clinical trial participants. Figure 16 shows the anti-HIV activity of vaginal fluid samples collected 4 and 24 hours after insert application. Figure 17 shows the anti-HSV (herpes) activity of vaginal fluid samples from two clinical trial participants collected at the start of the study (V2) and subsequently after treatment (V3). Detailed Description of the Invention The terms treatment, treated, treat, therapy, therapeutic, and similar terms are used here to refer generally to achieving a desired pharmacological and / or physiological effect. The effect may be prophylactic in terms of the complete or partial prevention of a disease or its symptoms, and / or therapeutic in terms of the stabilization or partial or complete cure of a disease and / or adverse effects attributable to the disease. Treatment, as used here, covers any treatment of a disease in a subject and includes: (a) preventing a disease or symptom from occurring in a subject who may be predisposed to the disease or symptom, whether or not they have been diagnosed with it; (b) inhibiting the symptom of the disease, in this case, halting its development; or (c) relieving the symptom of the disease, in this case, causing the disease or symptom to regress. The term pharmaceutically acceptable carrier, as used herein, refers to any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents, and absorption retarders for pharmaceutically active substances that are sufficiently known in the art. The term pharmaceutically active ingredient, pharmaceutical, or agent, as used herein, includes a pharmaceutically acceptable and therapeutically effective compound, pharmaceutically acceptable salts, stereoisomers and mixtures of stereoisomers, solvates (including hydrates), polymorphs, or prodrugs thereof. Unless otherwise indicated, when a drug is referred to in the descriptions of the various embodiments of the invention, the reference includes the base drug, pharmaceutically acceptable salts, stereoisomers and mixtures of stereoisomers, solvates (including hydrates), polymorphs, or prodrugs thereof. Except to the extent that any conventional means or agent is incompatible with the agent, its use in therapeutic pharmaceutical compositions is contemplated. Complementary compounds or biological pharmaceutical products may also be incorporated into the pharmaceutical compositions. As used herein, the term excipient refers to additives used to convert a pharmaceutical agent into a form suitable for its intended purpose. For the pharmaceutical compositions of the present invention suitable for administration to a human being, the term excipient includes the excipients described in the MANUAL OF PHARMACEUTICAL EXCIPIENTS, American Pharmaceutical Association, 2nd Ed. (1994), which is incorporated herein in its entirety. The term excipients is intended to include fillers, binders, disintegrants, lubricants, solvents, suspending agents, dyes, extenders, surfactants, auxiliaries, and the like. The term therapeutically effective amount refers to an amount of an agent described herein, which is effective in preventing, improving, treating, or delaying the onset of a disease or condition. The pharmaceutical compositions of the inventions may be administered to any animal that can experience the beneficial effects of the agents of the invention. Such animals include humans and non-humans, such as primates, pets, and farm animals. The term bioadhesive material refers to a material that improves the adhesion of a pharmaceutical composition to a mucosal or similar biological surface compared to the adhesion of the pharmaceutical composition without the bioadhesive material. Non-limiting examples of bioadhesive materials include bioadhesive polymers such as povidone and hydroxypropylcellulose. The term sustained release refers to a form of dosage in which the release rate of the active ingredient is spread out over a period of time (e.g., 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes) as opposed to immediate release (less than one minute) of the active ingredient. This application provides for on-demand solid dosage forms for the vaginal or rectal administration of antiviral drugs. The vaginal and rectal routes of administration offer unique anatomical and physiological advantages, such as: (a) the potential to increase local or systemic absorption of drug substances due to the large surface area and abundant blood supply, and (b) the vaginal or rectal route of drug delivery bypasses hepatic and intestinal first-pass metabolism. Consequently, antiviral drugs administered vaginally or rectally may provide improved bioavailability and a reduction in dosage level compared to other routes, such as oral dosage forms.Therefore, this application provides a cost-effective, affordable, portable, and easy-to-use technology for the prevention and / or treatment of various viral diseases, such as HIV, through the administration of several antiviral drugs. According to certain modalities, the described dosage forms comprise (a) NRTI: Tenofovir Alafenamide Fumarate (TAF) salt form, and (b) Integrase Inhibitor: Elvitegravir (EVG) in the form of an on-demand insert for HIV prevention. Currently, no such product is available. Significantly, from a drug delivery perspective, topical inserts are versatile, economical, stable, and well-suited for event-driven, on-demand administration of antiretroviral drugs (ARVs) and other small molecules. The present application, according to certain embodiments, provides dosage forms that exhibit sufficient mucoadhesive properties to adhere to the vaginal or rectal mucosa and provide the release of the pharmaceutically active ingredients. Although the present application describes sustained-release compositions in detail, other release profiles such as immediate release, pulsed release, and prolonged release may also be useful according to particular embodiments. The sustained-release vaginal or rectal mucoadhesive dosage form may comprise a combination of antiviral pharmaceutically active ingredients. According to certain embodiments, the solid dosage form may exhibit a mucoadhesive release strength of at least 0.1 N, more particularly at least 0.2 N, 0.25 N, or in some cases, 0.3 N when measured according to the test method described herein using porcine vaginal mucosa. The dosage form provides sustained release of the antiviral active pharmaceutical ingredient(s) while incorporating mucoadhesive properties into the vaginal or rectal wall, thus minimizing discomfort for the user and ensuring sustained release. The dosage form is typically for local topical administration. Application of the dosage form can be performed by the user. In some formulations, the dosage form is referred to as an insert, as it is inserted into the vaginal or rectal cavity. Examples of pharmaceutically active ingredients include, but are not limited to, antivirals (entry inhibitors, fusion inhibitors, nucleoside analogue reverse transcriptase inhibitors [NRTIs], nucleotide analogue reverse transcriptase inhibitors [NtRTIs], non-nucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors, protease inhibitors, capsid inhibitors and large molecule biologics, including, but not limited to, DNA / RNA, antibodies, proteins, peptides and adeno-associated virus [AAV] vectors, lyophilized dry-mixed large molecule biologics / excipients), antibacterial agents, antifungal agents, spermicides, hormones, contraceptive agents, micronutrients (such as vitamins, minerals) and / or combinations thereof.Depending on the formulation, dosage forms may also contain an antibiotic to prevent sexually transmitted infections (STIs) or genital or rectal infections, such as those caused by bacterial vaginosis, trichomoniasis, syphilis, chlamydia, gonorrhea, and Treponema species, as well as viral infections caused by HIV, HSV, and HBV. Examples of useful antibiotics include, but are not limited to, tetracyclines, macrolides, nitroimidazoles, and lincosamides. Antibiotics that may be particularly helpful include doxycycline (in the form of doxycycline hyclate, doxycycline anhydrous, or doxycycline monohydrate), azithromycin, metronidazole, tinadazole, secnidazole, and clindamycin. According to some formulations, the dosage form contains a combination of antiviral drugs and, in some cases, a combination of (a) an NRTI and (b) an integrase inhibitor. Examples of NRTIs include, but are not limited to, adefovir, adefovir dipivoxil, emtricitabine, tenofovir, tenofovir alafenamide, tenofovir alafenamide fumarate, tenofovir alafenamide hemifumarate, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir disoproxil hemifumarate, abacavir, abacavir sulfate, alovudine, apricitabine, censavudine, didanosine, elvucitabine, festinavir, fosalvudine tidoxil, fozivudine tidoxil, lamivudine, phosphazide, stavudine, zalcitabine, and zidovudine. Examples of integrase inhibitors include, but are not limited to, elvitegravir, curcumin, chicoric acid, 3,5-dicaffeoylquinic acid, auryntricarboxylic acid, caffeic acid phenethyl ester, tirfostine, quercetin, raltegravir, dolutegravir, cabotegravir and derivatives thereof. Depending on the formulation, the dosage form contains a combination of (a) tenofovir alafenamide and (b) elvitegravir (EVG). In certain formulations, tenofovir alafenamide is in the fumarate salt (TAF) form. Depending on the formulation, the dosage form may also contain an antibiotic in addition to TAF and EVG. According to some formulations, the dosage form may contain from approximately 1.5% to approximately 15% by weight of the pharmaceutically active ingredients, and more particularly from approximately 2% to approximately 10% of the pharmaceutically active ingredients. According to some formulations, the dosage form may contain a combination of pharmaceutically active ingredients, where each individual pharmaceutically active ingredient is present in an amount from approximately 1% to approximately 12%, more particularly from approximately 2% to approximately 8%, and even more particularly from approximately 1.6% to approximately 4.8% by weight. According to certain formulations, the dosage form contains a combination of (a) the salt form of tenofovir alafenamide fumarate (TAF) and (b) elvitegravir (EVG).In some formulations, the dosage form may contain tenofovir alafenamide fumarate (TAF) in an amount ranging from approximately 2% to approximately 8% of TAF as free base (equivalent to 2.24% to 8.96% of tenofovir alafenamide fumarate salt base) and approximately 1.6% to approximately 4.8% of elvitegravir (EVG). Antibiotics, when included in the dosage form, can be used in sufficient quantities to achieve the desired therapeutic effect. Typically, antibiotics can be included in an amount from approximately 2% to 30%, more particularly from approximately 5% to 25%, and in certain cases, from approximately 10% to 20% by weight of the dosage form. The dosage forms described herein may contain a combination of pharmaceutically acceptable carriers and / or excipients that provide the desired mucoadhesive properties and sustained release of the active ingredient. Excipients typically used include, but are not limited to, binders, bioadhesive polymers, disintegrating agents, diluents, bulking agents, hydrophilic excipients, and lubricants. Some excipients may provide one or more functional roles in the dosage form. Examples of binders include, but are not limited to, povidone (polyvinylpyrrolidone, PVP), sodium carboxymethylcellulose (NaCMC), carboxymethylcellulose (CMC), starch, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose (CMC), hydroxypropylcellulose (HPC), acacia, tragacanth, and gelatin. In some embodiments, the binder is a povidone, such as povidone K29 / 32, povidone K30, povidone K90, povidone K15, povidone K17 PF, and povidone K25. Combinations of binders may also be used. In some embodiments, the binder is also a bioadhesive polymer, which contributes to the mucoadhesive properties of the dosage form. In some embodiments, the binder also functions as a disintegrant. According to certain modalities, the binder may be present in an amount from approximately 0.5% to 8%, more particularly from approximately 1% to 5% and, in certain cases, from approximately 2% to 4% by weight of the dosage form. Examples of bioadhesive polymers include, but are not limited to, hyaluronic acid, sodium hyaluronate, carrageenan, sodium alginate, and PEG. In certain formulations, the bioadhesive polymer is a PEG, specifically PEG 6000 or PEG 8000. Combinations of bioadhesive polymers may also be used. Depending on the formulation, the bioadhesive polymer may be present in amounts ranging from approximately 5% to 30%, more specifically from approximately 7.5% to 25%, and in some cases, from approximately 10% to 20% by weight of the dosage form. Examples of disintegrating agents include, but are not limited to, starch, sodium starch glycolate, povidone and calcium silicate, polysorbates (such as polysorbate 20 or 80) and poloxamers (such as poloxamer 188 or 207). In one particular embodiment, the disintegrating agent is a poloxamer, more particularly poloxamer 188. Combinations of disintegrating agents may also be employed. According to certain embodiments, the disintegrating agent is water-soluble. According to some embodiments, the dosage form is free of water-insoluble disintegrating and / or superdisintegrating agents, such as crospovidone or croscarmellose. According to certain embodiments, the disintegrating agent may be present in an amount from approximately 0.5% to 4%, more particularly from approximately 1% to 3%, and in some cases from approximately 1.5% to 2.5% by weight of the dosage form. Examples of lubricants include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, glyceryl monostearate, sodium stearyl fumarate, colloidal silicon dioxide, and talc. Combinations of lubricants may also be used. Depending on the formulation, the lubricant may be present in an amount from approximately 0.2% to 4%, more specifically from approximately 0.5% to 3%, and in some cases from approximately 1% to 2% by weight of the dosage form. Examples of fillers (also known as bulking agents or diluents) include, but are not limited to, starches, maltodextrins, polyols (such as lactose), sugar alcohols, and celluloses. Combinations of fillers may also be used. Depending on the formulation, the filler may be present in an amount from approximately 5% to 90%, more particularly from approximately 10% to 75%, and in some cases from approximately 20% to 60% by weight of the dosage form. The dosage forms provided herein may include lactose and / or sugar alcohols. Lactose may be used in anhydrous or hydrated (e.g., monohydrate) form. Depending on the formulation, lactose may be present in an amount from approximately 25% to 75%, more particularly from approximately 30% to 70%, and in some cases from approximately 40% to 60% by weight of the dosage form.Examples of sugar alcohols that may be used include, but are not limited to, mannitol, glycerol, erythritol, xylitol, sorbitol, isomalt, maltitol, lactitol, and mixtures thereof. Depending on the formulation, sugar alcohols may be present in amounts ranging from approximately 5% to 30%, more specifically from approximately 7.5% to 25%, and in some cases from approximately 10% to 20% by weight of the dosage form. Examples of hydrophilic excipients include, but are not limited to, hyaluronic acid, maltodextrin, dextrin, cyclodextrin, vitamin E, TPGS, Pluronics, amino acids, gelatins, polyethylene glycols including, but not limited to, polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000), polyethylene glycol 8000 (PEG 8000), poly(ethylene oxide) (PEO), poly(vinylpyrrolidone) (PVP), cellulose ethers including, but not limited to, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethylcellulose (HEC), sodium carboxymethylcellulose (NaCMC), methylcellulose (MC), and mixtures thereof. Combinations of hydrophilic excipients may also be used. According to certain formulations, hydrophilic excipients may be present in an amount from approximately 0.5% to 25%, more particularly from approximately 10% to 20%, and in certain cases from approximately 5% to 15% by weight of the dosage form. According to some formulations, the solid dosage form may have a weight of approximately 0.1 to approximately 2.0 g, more particularly from approximately 0.2 to approximately 1.0 g, and even more particularly from approximately 0.25 to approximately 0.75 g. In some cases, the nominal average weight may be approximately 0.5 g (0.475 to 0.525 g). According to some models, the solid dosage form can have a length of approximately 10 mm to 25 mm, a width of approximately 5 mm to 20 mm, and a thickness of approximately 2 mm to 10 mm. The shape of the dosage form is not particularly limited; it can be a circle, oval, rectangle, square, triangle, capsule, bullet, diamond, or almond. According to some formulations, the solid dosage form has a pH of 3 to 7.5 after dissolving in a volume of water of 0.5 to 10 ml and is compatible with the pH of the vaginal and rectal compartment after dissolving. Although the present application exemplifies solid dosage forms, other dosage forms such as gels, foams, films, intravaginal rings, vaginal douches, enemas, suppositories, tablets, transdermal patches, suspensions, emulsions, and weights may also be useful. According to certain formulations, the dosage forms provide topical administration of the pharmaceutically active ingredient. Particularly useful compositions are those in which a tenofovir prodrug is combined with an integrase inhibitor, and more specifically, where TAF is combined with EVG or TAF is combined with other integrase inhibitors such as dolutegravir and cabotegravir, as well as with integrase inhibitor prodrugs. Methods of Use The compositions and dosage forms described herein can be used in the treatment and / or prevention of various diseases, such as HIV, HSV, and HBV. In certain modalities, a method for treating or preventing a viral infection in a subject comprises administering to the subject a pharmaceutical composition or solid dosage form as described herein. This application describes the potential benefits of combining TAF with EVG in a formulation such as a vaginal or rectal insert for the prevention or treatment of HIV, HSV, and HBV for both past and present exposures. The efficacy of the composition for the prevention or treatment of HIV, HSV, and HBV for both past and present exposures is unexpected and surprising.In some modalities, a method for treating or preventing a viral infection, as well as for treating another infection, such as a bacterial or fungal infection, in a subject comprises administering to the subject a pharmaceutical composition in a solid dosage form as described herein. Infections that may be treated include, but are not limited to, chlamydia, gonorrhea, bacterial vaginosis, trichomoniasis, and syphilis. Manufacturing Process The solid dosage forms described here can be produced using conventional manufacturing processes and processing steps. An exemplary process for producing these solid dosage forms is provided below. The APIs can be passed through a sieve (e.g., #20 mesh) and loaded into a mixer, such as a V-shaped SHEL / TOTE mixer. The excipients can be sieved (e.g., through a 045R sieve and a round impeller at approximately 1250 rpm) and then loaded into the mixer. The components can be blended for a period of time and then discharged into a polyethylene-lined container. The mixture can then be transferred to a tablet press for compression. The pressed tablets are then collected in a polyethylene-lined container, and the samples are analyzed for weight, thickness, and hardness. The pressed material can then be passed through a sieve (e.g., through a 045R sieve and a round impeller at approximately 1250 rpm), and then approximately half of the pressed material is loaded into the mixer.The lubricant and any remaining ingredients are loaded into the mixer, followed by the remaining half of the pressed material. The resulting mixture is blended, samples are taken, and the mixture is then discharged into a polyethylene-lined container. This mixture is fed into a tablet press, and the samples are tested for dissolution properties. The resulting solid dosage forms (inserts) are dedusted and sieved before being collected in triplicate in polyethylene-lined buckets, which have two desiccant pads placed between the outer and inner polyethylene linings. The resulting inserts are stored and sampled for testing. Examples The following examples are presented for illustrative purposes only and are not intended to be limiting. The osmolality of the TAF / EVG vaginal insert was studied in relation to placebo (no active drugs) and P02 (40 / 24 mg TAF / EVG) and P03 (20 / 16 mg TAF / EVG) in artificial vaginal fluid at a pH of 4.2. The results are summarized in Table 1 below, which indicates an acceptable osmolality range. Table 1: The osmolality of the Placebo, P02 and P03 in the artificial vaginal fluid was measured at different time intervals and is presented below. Placebo Time (mOsm / L) PO2 (mOsm / L) PO3 (mOsm / L) 0 212 212 213 15 541 425 464 30 785 491 639 45 882 635 772 60 1062 560 664 Table 2 below provides exemplary formulations containing two antiviral drugs: tenofovir alafenamide and elvitegravir. Three formulation compositions of the TAF / EVG insert (F1, F2, and F3) were manufactured and met the criteria for hardness, friability, and in vitro release in simulated vaginal fluids. Hardness values ​​typically range from 5 to 8. Friability is typically less than 1.0%. The dosage form in this example was an uncoated, white to off-white, bullet-shaped insert. Table 2. Examples of Manufacturing Processes (formulations F1-F3 in three concentrations) pcc^nn / Lznz / E / YiAi Ingredients Formulation ID Fl F2 F3 % Weight (mg) % Weight (mg) % Weight (mg) 1 Fumarate de Alafenamida de Tenofovir (TAF) 8.96 44.8* 4.48 22.4** 2.24 11.2** 2 Elvitegravir (EVG) 4.8 24 3.2 16 1.6 8 2 Povidona (K- 29 / 32) 4 20 4 20 2 10 4 Magnesium stearate 1 5 1 5 0.5 2.5 5 Poloxámero 188 2 10 2 10 1 5 Ingredients Formulation ID F1 F2 F3 % Weight (mg) % Weight (mg) % Weight (mg) 6 Lactosa monohydrate 49.88 249.4 52.92 264.6 26.46 132.3 7 Mannitol 14.36 71.8 17.4 87 8.7 43.5 8 PEG 8000 15 75 15 75 7.5 37.5 Total 100 500* 100 500* 100 500* pcc^nn / Lznz / E / YiAi * Equivalente a 40.0 mg de base libre de Alafenamida de Tenofovir (El) * * Equivalente a 20.0 mg de base libre de Alafenamida de Tenofovir (F2) * ** Equivalente a 10.0 mg de base libre de Alafenamida de Tenofovir (F3) EVG showed potent anti-HIV activity in a cervical vaginal (CV) tissue explant study when applied up to 24 hours before or after HIV exposure. The antiviral effect was dose-dependent, with EVG doses of 1 and 10 pg / ml providing complete protection at all pre- and post-exposure time points, while 0.1 pg / ml appeared to be unable to provide complete protection against HIV at pre-exposure settings, as shown in Table 3 and Figures 1A-1C. Table 3: Average percentage of protection of EVG against pcc^nn / Lznz / E / YiAi HIV infection % protection of mean AUC against HIV control EVG concentration 0.1 pg / ml 1 pg / ml 10 pg / ml Pre-exposure Oh 34.5% 99.97% 100% 7h 21.53% 99.1% 100% 24h 44.8% 99.51% 100% 4h 86% 99.56% 100% 9h 85.85% 100% 100% 14h NT NT 100% 24h NT NT 100% Co-exposure virus and EVG virus and API aggregated together 97.56% 100% NT Percentage of protection determined from explants of 3-9 donors using the following equation: 100(explants treated with AUC * 100 / explants not treated with AUC) . AUC: area under the infection curve. NT: not tested. The mean EVG concentration in CV tissues after 4 h of exposure to 10 and 1 pg / ml of EVG, both of which completely inhibited HIV infection in CV explant tissues were: 13,381 ng / g and 1,150 ng / g, respectively. Based on the data, it can be extrapolated that tissue concentrations of EVG of >1000 ng / g provided 100% HIV prophylaxis. (Figure 2). This application provides solid dosage forms in which all tenofovir prodrug forms (e.g., tenofovir disoproxil fumarate (TDF); tenofovir alafenamide fumarate (TAF)) can be used alone or in combination with an integrase inhibitor such as EVG. These tenofovir prodrugs in in vitro cell model studies showed enhanced potency pre-HIV exposure (Figure 3) and post-HIV exposure (Figure 4) when combined with EVG, demonstrating that an expanded window of prophylactic activity can be achieved by combining the tenofovir prodrug and EVG. Infection rates were significantly lower for the combination of TAF with EVG and TDF with EVG in both pre- and post-HIV exposure. TAF, TFV, acyclovir (ACV), and TDF were found to show enhanced activity against HSV. The prodrugs TFV and TFV exhibit anti-HSV activity, and TAF was found to be the most potent (Figure 5). The 20 / 16 mg TAF / EVG insert is a stable product, as shown by its 6-month stability at 30°C / 75% RH and 40°C / 75% RH for the lead formulation containing TAF / EVG (20 / 16 mg) (P03) with 3 g of silica gel desiccants in HDPE bottles containing 20 inserts each. The results are summarized in Table 4 and Table 5. Table 4. Stability of the 20 / 16 mg TAF / EVG insert Pilot Batch (P03 - 30°C / 65% RH) pcc^nn / Lznz / E / YiAi Parameters T=0M T=1M T=3M T=6M Physical Appearance (n=10) Pass Pass Pass Pass Hardness (kg) (n=10) 5.98 ± 0.34 5.86 ± 0.51 4.58 ± 0.55 6.01 ± 0.49 Friability (%) (n=13) 0.58 0.33 0.55 0.49 Content Assay (%) - TAF (n=10) Target (90110.0%) 97.36 1 0.78 102.40 1 0.58 102.87 ± 0.49 91.41 ± 0.69 Content Assay (%) - EVG (n=10) Target (90110.0%) 95.97 ± 0.39 100.82 ± 0.42 97.841 0.95 95.531 1.95 RC (%)* (n=10) ND** ND** ND** ND** Moisture Content (%) (n=5) 0.20 ± 0.02 0.02 ± 0.00 0.681 0.16 0.19 1 0.00 Dissolution (Customer) (min) (n=6) 60 60 60 60 Disintegration (min) (n=6) 15 15 20 14 * RC (%): Total impurities (related compounds, RC1, RC2 and RC3). ** ND: Not detectable. Table 5. Stability of TAF / EVG20 / 16 mg insert Pilot batch (P03 - 40°C / 75% RH) ccc^nn / Lznz / B / YiAi Parameters T=0M T=1M T=2M T=3M T=6M Physical Appearance (n=10) Pass Pass Pass Pass Pass Hardness (kg) (n=10) 5.98 ± 0.34 5.75 ± 0.42 5.74 ± 0.41 6.42 ± 0.85 6.01 ± 0.60 Friability (%) (n=13) 0.58 0.8 0.51 0.65 0.65 Content Test (%) -TAF (n=10) 97.36 ± 0.78 100.28 ± 1.02 102.00 ± 0.77 98.20 ± 1.60 34.00 ± 0.74 Content Test (%) -EVG (n=10) 95.97 i 0.39 100.57 ± 0.47 100.12 ± 0.40 93.98 ± 0.78 34.58 1 0.30 RC (%)* (n=10) ND** ND** ND** ND** ND** Moisture Content (%) (n=5) 0.20 ± 0.02 0.05 ± 0.02 0.07 ± 0.02 0.29 ± 0.18 0.17 ± 0.00 Dissolution (Customer) (min) (n=6) 60 60 60 60 60 Disintegration (min) (n=6) 15 16 15 20 25 *RC (%): Total impurities (related compounds, RC1, RC2 and RC3). **ND: Not detectable. Stability test The TAF / EVG insert showed excellent stability at both 30°C and 40°C and is expected to have a minimum shelf life of two years when stored at 30°C or lower (see Figures 6 and 7). The stability of TAF in the described formulation is particularly unexpected given that the drug is typically prone to degradation over time. Cumulative percentage dissolution study of TAF / EVG inserts The dissolution of the TAF / EVG insert was performed using the USP 2 apparatus (Paddle). The method consisted of six dissolution vessels. For this purpose, six inserts were weighed and the weights of the individual inserts were recorded. Each insert was placed on a stainless steel stage and inserted into the corresponding dissolution vessel, and the timer was immediately initialized. Using a syringe equipped with a stainless steel cannula with a 10 pm full-flow filter, a 5 mL portion of the solution was withdrawn from each vessel from a zone midway between the surface of the dissolution medium and the top of the paddle, no less than 1 cm from the vessel wall, at 5, 10, 15, 30, 45, 60 minutes and indefinitely (an additional 15 minutes at 250 rpm), and injected into the HPLC column after dilution with diluent.To prepare one liter of diluent, 500 mL of mobile phase A were added to 500 mL of acetonitrile (ACN) (mobile phase B), mixed thoroughly, and degassed before use. A gradient method was used, consisting of mobile phase A (20 mM phosphate buffer solution at pH 2.5) and mobile phase B (100% ACN). The following HPLC parameters and dissolution method were used to analyze the percentage dissolution of tenofovir alafenamide and envitegravir from TAF / EVG inserts stored under stable conditions of 30°C / 65% RH (at months 0, 3, 6, and 9) and 40°C / 75% RH (at months 0, 3, and 6). HPLC parameters Column: Phenomenex Kinetex C-18, 4.6 x 150 mm, 2.6 pm or equivalent. Column Temperature: 30°C Detection: UV at 260 nm Injection Volume: 10 pL Flow Rate: 1.2 ml / min Duration: 16 minutes Mobile Phase A: 20 mM KH2PO4 in Water, pH 2.5 Mobile Phase B: 100% Acetonitrile Dissolution Apparatus Parameters Apparatus: USP 2 apparatus (Paddle) Dissolution Temperature: 37.0 + 0.5°C pcc^nn / Lznz / E / YiAi Rotation Speed: 50 rpm Dissolution Volume: 900 pL Dissolution Medium: 50 mM phosphate buffer solution / 0.25% SDS (pH = 6.0) The dissolution profiles of the TAF / EVG insert from several stability-aged samples showed similar dissolution for the TAF and EVG drugs compared to time zero, establishing additional potential benefits of formulations produced in accordance with the present for HIV prevention (see Figures 8 to 11). Mucoadhesive Properties The bioadhesive properties were evaluated using porcine vaginal tissue by measuring the peel strength [(Table 6 and Figure 12)], and were compared with mucin solution as a control (Table 7 and Table 8). The peel strength of ~0.3 N (300 mN) for a dosage form insert with porcine vaginal tissue versus the peel strength of ~0.01 N (10 mN) of the insert with mucin solution shows a significant difference; thus, the dosage form insert described here exhibits strong mucoadhesive properties. The mucoadhesive properties of the TAF / EVG insert with porcine vaginal mucosa were studied using the Mechanical Test method as briefly described below: The mechanical testing apparatus consisted of two flat metal plates connected to a load cell, capable of measuring crush / tensile strength up to 50 Newtons (N). A tablet die with a diameter comparable to that of the sample was placed on the lower plate of the mechanical testing apparatus. A small segment of porcine vaginal tissue (2 x 2 cm) was attached to the upper metal plate with cyanoacrylate adhesive and soaked in 50 mL of SVF for 30 seconds before analysis. The test sample was hermetically sealed within the tablet die cavity. The insert was moistened by adding 50 pL of SVF drop by drop with a pipette, and the top of the mechanical tester was manually lowered close enough to the insert and then automatically lowered at a speed of 5 mm / min (~0.1 mm / sec) to allow contact with the moistened insert for 60 seconds with a compressive force of 5N.The force required to detach the vaginal tissue from the insert was measured as the detachment force in Newtons (N). The samples tested in this study were CONRAD P03 (20 / 16 mg TAF / EVG insert) and CONRAD P04 (placebo insert). Table 6: Mechanical Testing and Bioadhesion Studies Type of Weight Detachment Force (N) Detachment Force Tissue Weight Force (N) Average Detachment Force Tissue Weight Force (N) Weight of Tissue (dry) in Newtons (N) Plate Tare (g) (g) 5 Sample Sample CONRAD- P04 P04-1 21.486 0.995 0.010 0.383 0.373 0.344 ± 0.036 (Placebo Insert) P04-2 21.482 0.533 0.005 0.308 0.303 10 P04-3 21.482 0.854 0.008 0.363 0.355 CONR P03-1 21.482 0.650 0.006 0.368 0.362 POS (TAF / Insert P03-2 21.482 0.857 0.008 0.280 0.272 0.317 ± 0.188 15 EVG) P03-3 21.482 0.769 0.008 0.358 0.350 The mucoadhesive properties of the mucin solution were evaluated as described below. Different concentrations of mucin solutions (20%, 10% and 1.5% w / v) were prepared by dissolving mucin powder in SVF under agitation overnight at 37°C. The mechanical testing apparatus was used to analyze the peel strength for this study. The samples tested in this study were CONRAD P03 (20 / 16 mg insert of TAF / EVG) and CONRAD P04 (placebo insert). Distilled water was used as a control for all three tests. Test A: Immersion of the insert in mucin solutions (20, 10, and 1.5% w / v) (n = 3) - The insert was fully immersed in the mucin solutions. The insert was held with the upper portion of the mechanical tester and lowered manually to allow contact with the liquid for 30 seconds. The peel strength was measured using the computer program (Shimadzu Trapezium2 Version 2.22c). Test B: Insert touching the surface of mucin solutions (20, 10, and 1.5% w / v) (n = 3) - The insert was made to touch the surface of the mucin solutions. The insert was held with the upper portion of the mechanical tester and lowered manually to allow contact with the liquid for 30 seconds. The detachment force was measured using the computer program (Shimadzu Trapezium2 Version 2.22c). Table 7: Insert immersed in mucin solutions ccc^nn / ίζηζ / Β / γίΛΐ Sample Mean Forces (N) Average Force (N) P03-1 Water 0.012 0.010 ± 0.004 P03-2 Water 0.005 P03-3 Water 0.013 P03-1 1.5% Mucin 0.011 0.014 ± 0.006 pcc^nn / Lznz / E / YiA Sample Mean Forces (N) Average Force (N) P03-2 1.5% Mucin 0.01 P03-3 1.5% Mucin 0.02 P03-1 10% Mucin 0.01 0.012 ± 0.004 P03-2 10% Mucin 0.009 P03-3 10% Mucin 0.016 P03-1 20% Mucin 0.013 0.013 ± 0.002 P03-2 20% Mucin 0.011 P03-3 20% Mucin 0.014 Table 8: Insert touches the surface of the mucin solutions Sample Mean Forces (N) Average Force (N) P03-1 Water 0.013 0.012 ± 0.008 P03-2 Water 0.004 P03-3 Water 0.02 P03-1 1.5% Mucin 0.01 0.011 ± 0.008 P03-2 1.5% Mucin 0.009 P03-3 1.5% Mucin 0.014 P03-1 10% Mucin 0.011 0.009 ± 0.002 P03-2 10% Mucin 0.009 Sample Mean Forces (N) Average Force (N) P03-3 1.5% Mucin 0.014 P03-1 10% Mucin 0.011 0.009 ± 0.002 P03-2 10% Mucin 0.009 P03-3 10% Mucin 0.007 P03-1 20% Mucin 0.011 0.010 ± 0.001 P03-2 20% Mucin 0.009 P03-3 20% Mucin 0.009 pcc^nn / Lznz / E / YiAi Based on the mucoadhesion experiments performed, the 20 / 16 mg TAF / EVG inserts have shown unexpectedly good mucoadhesive behavior. Additional data on dissolution and disintegration profiles were also generated for the dosage forms described herein. The 20 / 16 mg TAF / EVG insert (CONRAD P03) was evaluated for its disintegration / dissolution profiles by visual observation when exposed to 5 ml of simulated vaginal fluid (SVF, pH 4.3 at 37°C) and 5 ml of simulated rectal fluid (phosphate-buffered saline [PBS, pH 7.2 at 37°C]). Five ml of SVF or PBS (preheated to 37°C) was added directly to the top of the insert, and images were captured at predetermined time intervals of 0, 5, 15, 30, 45, 60, 90, 120, and 150 min using an AmScope digital polarized microscope camera (MU1000). In both SVF and PBS solutions, the dissolution / disintegration of the form The solid dosage form was driven by a surface erosion mechanism and the solid dosage form was eventually completely dissolved / disintegrated without residue.The surface erosion mechanism was unique to the TAF / EVG insert. Figures 13 and 14 show the dissolution and disintegration over time for the solid dosage forms in simulated vaginal fluid and simulated rectal fluid, respectively. Surface erosion provided significant advantages over bulk erosion. The bulk erosion process was dependent on the volume of the dosage form, and thus, due to degradation, the volume of the dosage form decreased, causing the erosion rate to slow down over time. Therefore, bulk erosion rates were difficult to control. In contrast, solid dosage forms according to the present invention exhibited surface erosion, which is advantageous because the erosion process was constant and independent of the dosage form volume. The surface erosion associated with the present invention was unexpected and provided benefits such as consistent and robust dissolution results that were not obtained with volume erosion dosage form formulations. The solid dosage form inserts appeared to disintegrate / dissolve through surface erosion, as visually observed and shown in the images, in SVF (pH 4.3) and PBS (pH 7.2). They dissolved completely in both SVF and PBS solutions, with no residue observed after complete dissolution. Stability was unexpectedly excellent. The mucoadhesive properties of the mucin (~0.018 N ± 0.009) tested with one insert were significantly lower compared to TAF / EVG inserts, with an average peel strength against porcine vaginal tissue (~0.317 N ± 0.188). There were no changes in the dissolution profiles of the TAF / EVG inserts when stored at 30°C / 65% RH and 40°C / 75% RH compared to the initial dissolution profile.The TAF / EVG inserts were found to be stable based on stability study data and were projected to remain stable for a minimum of 2 years when stored at 30°C or below. Overall, these results are a good indicator of the TAF / EVG inserts' ability to bioadhesive to the vaginal mucosa for effective local delivery of TAF (tenofovir alafenamide fumarate) and EVG (elvitegravir) to the vaginal mucosa. Table 9 provides an exemplary insert formulation according to one aspect of the present invention. The composition exhibited efficacy in the non-human primate model. Table 9 Compositions of TAF / EVG, 20 mg / 16 mg of ccc^nn / lzoz / b / yiai formulation insert Materials %w / w per Insert Weight per Insert (500 mg) Functional Roles Pharmacopoeial Grade Tenofovir alafenamide fumarate salt form (TAF) * 4.48 22.4* API GMP Elvitegravir (EVG) 3.20 16.0 API GMP Povidone (K-29 / 32) 4.00 20.0 Binder, Disintegrant USP Poloxamer 188 2.00 10.0 Disintegrant NF, EP, JPE Anhydrous lactose 52.92 264.6 Diluent NF Mannitol 16.90 84.5 Bulking Agent USP PEG 8000 15.00 75.0 Lubricating / bioadhesive polymer NF Magnesium stearate 1.50 7.5 Lubricant NF * 22.4 mg of Tenofovir Alafenamide Fumarate (TAF) salt is equivalent to 20 mg of Tenofovir Alafenamide Fumarate (TAF) free base. DEMONSTRATION OF ANTIVIRAL ACTIVITY IN HUMANS The solid dosage forms of TAF / EVG described in Table 9 were tested in women in the CONRAD 146 clinical trial (ClinicalTrials.gov number NCT03762772). The women (N = 16) self-administered using a single vaginal insert and provided cervical tissue and vaginal fluid samples 4 and 24 hours post-dose for assessment of anti-HIV and anti-HSV activity. Figures 15A and 15B show examples of complete protection against HIV infection ex vivo in baseline and post-treatment cervical tissue samples from two clinical trial participants. These data showed that human genital tissues are protected against HIV infection after topical application of TAF and / or EVG when solid dosage form inserts are administered according to this application. Figure 16 shows the anti-HIV activity of vaginal fluid samples collected 4 and 24 hours after insert application. Surprisingly, the inserts inhibited HIV infection even 24 hours after administration, providing long-lasting protection. Figure 17 shows the anti-HSV (herpes) activity of vaginal fluid samples from two clinical trial participants collected at baseline (V2) and post-treatment (V3). A significant decrease (downregulation of specific genes) in HSV replication was observed in HEC1A cells in the post-treatment V3 samples. This is believed to be the first time this phenomenon—the inhibition of herpes infection in genital tract cells—has been observed with human vaginal fluid samples exposed to TAF / EVG. TFV and TDF represent trial controls. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A pharmaceutical composition characterized in that it comprises: a. a therapeutically effective amount of one or more antiviral active pharmaceutical ingredients; and b. one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition provides a therapeutically effective amount of the antiviral active pharmaceutical ingredient to the vaginal or rectal mucosa when administered topically.

2. A pharmaceutical composition characterized in that it comprises: a. a therapeutically effective amount of one or more antiviral active pharmaceutical ingredients; and b. one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition provides a sustained release of the antiviral active pharmaceutical ingredient when administered as a vaginal or rectal insert.

3. A solid dosage form characterized in that it comprises: a. a therapeutically effective amount of one or more pharmaceutically active antiviral ingredients; and b. one or more pharmaceutically acceptable excipients, wherein the solid dosage form exhibits a mucoadhesive release strength of at least 0.1 N when measured according to the test method described herein with porcine vaginal mucosa.

4. The solid dosage form according to claim 3, characterized in that it comprises approximately 1.5% to approximately 15% by weight of antiviral pharmaceutically active ingredients.

5. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically active ingredients comprise an NRTI and an integrase inhibitor.

6. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically active ingredients comprise tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG).

7. The pharmaceutical composition according to claim 6 or the solid dosage form according to claim 6, characterized in that tenofovir alafenamide fumarate (TAF) is present in an amount from approximately 2% to 8% TAF as free base and elvitegravir (EVG) is present in an amount from approximately 1.6% to 4.8%.

8. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise povidone.

9. The pharmaceutical composition according to claim 8 or the solid dosage form according to claim 8, characterized in that the povidone comprises povidone K29 / 32, povidone K30 or a mixture thereof.

10. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise poloxamer 188 present in an amount of 0.5 to 4% by weight.

11. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise lactose present in an amount from approximately 25% to 75% by weight.

12. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form of claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise a sugar alcohol present in an amount from approximately 5% to 30% by weight.

13. The pharmaceutical composition according to claim 12 or the solid dosage form according to claim 12, characterized in that the sugar alcohol is selected from the group consisting of mannitol, glycerol, erythritol, xylitol, sorbitol, isomalt, maltitol, lactitol and mixtures thereof.

14. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise PEG present in an amount from approximately 5 to 30% by weight.

15. The pharmaceutical composition according to claim 1 or 2 or the solid pharmaceutical form according to claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise a lubricant selected from the group consisting of magnesium stearate, stearic acid, sodium stearyl fumarate, glycerol monostearate, silicon dioxide, talc, calcium stearate and mixtures thereof in the concentration in the range from 0.2 to 4% by weight, preferably from 0.5% to 3% by weight and most preferably from 1.0 to 2.0% by weight.

16. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that one or more pharmaceutically acceptable excipients comprise a hydrophilic excipient selected from the group consisting of hyaluronic acid, maltodextrin, dextrin, cyclodextrin, vitamin E TPGS, Pluronics, amino acids, gelatins, polyethylene glycols, poly(ethylene oxide) (PEO), poly(vinylpyrrolidone) (PVP), cellulose ethers and mixtures thereof.

17. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that it comprises: from approximately 1.5% to approximately 15% by weight of one or more antiviral pharmaceutically active ingredients; a binder in an amount from approximately 0.5% to approximately 8% by weight; a water-soluble disintegrant in an amount from approximately 0.5% to approximately 4% by weight; and a bioadhesive polymer in an amount from approximately 5% to approximately 30% by weight.

18. The pharmaceutical composition according to claim 17 or the solid dosage form according to claim 17, characterized in that: one or more antiviral pharmaceutically active ingredients comprise TAF and EVG; the binder comprises povidone; the water-soluble disintegrating agent comprises poloxamer 188; and the bioadhesive polymer comprises PEG 8000.

19. The pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to claim 3, characterized in that the dosage form further comprises an antibiotic.

20. The pharmaceutical composition according to claim 19 or the solid dosage form according to claim 19, characterized in that the antibiotic is selected from the group consisting of tetracyclines, macrolides, lincosamides, nitroimidazoles and mixtures thereof.

21. The pharmaceutical composition according to claim 19 or the solid dosage form according to claim 19, characterized in that the antibiotic is selected from the group consisting of doxycycline, doxycycline hylate, doxycycline anhydrous, doxycycline monohydrate, azithromycin, clindamycin, metronidazole, tinadazole, secnidazole and mixtures thereof.

22. A method for treating or preventing a viral infection in a subject characterized in that it comprises administering the pharmaceutical composition according to claim 1 or 2 or the solid dosage form according to any of claims 3-21 to the subject.

23. The method according to claim 22, characterized in that the viral infection is selected from the group consisting of HIV, HSV and HBV.

24. The method according to claim 22, characterized in that it further comprises treating another infection.

25. The method according to claim 24, characterized in that the other infection is selected from the group consisting of chlamydia, gonorrhea, bacterial vaginosis, trichomoniasis, and syphilis.

26. The method according to claim 24, characterized in that the viral infection is selected from the group consisting of HIV, HSV and HBV.